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SSRL Headlines Vol. 5, No. 11 May, 2005

Contents of this Issue:

Science Highlight — The Flip-side of MsbA Transporter Science Highlight — The First Known Native Cadmium Enzyme Found in Marine Phytoplankton X-rays Illuminate Ancient Archimedes Text Fallen Tree Interrupts User Operations for Several Days DOE Site Review of SLAC in Washington DC Keith Hodgson Named Deputy Director of SLAC DOE Review of LCLS Project and Proposed LUSI Project Director of OSTP Visits SLAC Axel Brunger Elected to the National Academy of Sciences Spring Meeting of the SLAC Scientific Policy Committee Machine Readable Passports Required for All Visa Waiver Program Travel as of June 26, 2005

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1.  Science Highlight — The Flip-side of MsbA Transporter
      (contact: Geoffrey Chang, gchang@scripps.edu)

	Overall structure of MsbA in complex with ADP, vanadate, Mg2+ and Ra lipopolysaccharide (LPS)

Membrane-bound transporter proteins have emerged as a key defense mechanism against potential toxins. The ATP-binding cassette (ABC) transporters belong to the largest known transporter gene family and translocate a variety of substrates including chemotherapy agents. Furthermore, the expression of the ABC multidrug transporters has been implicated in tumor cell resistance to anticancer therapy and the altered disposition (and associated toxicity) of chemotherapy drugs. In both humans and bacteria, ABC transporters have been implicated in antibiotic and cancer drug resistance. Therefore, ABC transporters represent key targets for the development of multidrug resistance reversal agents.

Using x-ray diffraction data collected at SSRL Beam Line 11-1 and at the ALS, researchers Geoffrey Chang and Christopher Reyes from The Scripps Research Institute have determined the 4.2 Å x-ray crystal structure of MsbA in complex with the transition state mimic ADP, vanadate (an analog of the g phosphate of ATP) and the human immunomodulatory substrate Ra lipopolysaccharide. Together with other MsbA structures, the current structure provides a framework for interpreting functional data concerning multidrug resistant ABC transporters. The structure supports a model involving a rigid-body troque of the two transmembrane domains during ATP hydrolysis and suggests a mechanism by which the nucleotide binding domain communicates with the transmembrane domain.

To learn more about this research published in the May 13, 2005 issue of Science see:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/MsbA.html or
http://www-ssrl.slac.stanford.edu/research/highlights_archive/MsbA.pdf

2.  Science Highlight — The First Known Native Cadmium Enzyme Found in Marine Phytoplankton
      (contact: Graham George, g.george@usask.ca)

Cadmium is known to be extremely toxic to mammals, and is generally viewed alongside mercury as an environmental problem and toxic element that is not used by nature in any way. A Brief Communication in the May 5 issue of the journal Nature shows that we need to revise our opinion of cadmium. The paper reports the purification and characterization of a previously unknown metalloenzyme from the marine diatom Thalassiosira weissflogii that specifically uses cadmium to achieve its

The marine diatom Thalassiosira weissflogii.

biological function. This is the first cadmium enzyme that has been discovered. The research team responsible includes former SSRL scientists Graham George and Ingrid Pickering (both now at the University of Saskatchewan) and colleagues from Woods Hole Oceanographic Institute, Sandia Laboratories, ExxonMobil Research and Engineering, and Princeton University. Colleagues on the team isolated the genes responsible for the cadmium enzyme, which also appear to be unique, and confirmed that the enzyme is a carbonic anhydrase. Carbonic anhydrases regulate levels of carbon dioxide within cells, and in plants catalyze the first step in the process of photosynthesis. All the other carbonic anhydrases that are known require zinc, and if the diatom is grown in seawater containing ample zinc then it makes an entirely different carbonic anhydrase that contains this element. But the surface waters of the oceans are extremely low in zinc, and this, together with the observation that adding cadmium allows them to grow, caused the researchers to look for a specific cadmium enzyme. X-ray absorption spectroscopy experiments performed at SSRL's BL7-3 allowed these researchers to gain initial structural understanding of the cadmium site and to relate this to that of analogous zinc-containing enzymes of terrestrial plants. The work reported in Nature indicates that cadmium plays a vital role in the global carbon cycle. Despite their microscopic size, marine phytoplankton are very numerous, and make up a significant fraction of the world's plants. They are thus responsible for a significant fraction of the cycling of atmospheric carbon dioxide through photosynthesis. Cadmium is needed for this (at least in diatoms), so it turns out that cadmium is environmentally essential instead of being just a toxic problem. Because many trace metals are found at low concentrations in the oceans, the researchers speculate that enzymes containing unusual metals may be more common in marine than in terrestrial organisms, and could be important for the cycling of trace metals in sea water.

To learn more about this research see:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/Cd-CA.html or
http://www-ssrl.slac.stanford.edu/research/highlights_archive/Cd-CA.pdf

3.   X-rays Illuminate Ancient Archimedes Text
      (contact: Uwe Bergmann, bergmann@slac.stanford.edu)

	Abigail Quandt, The Walters Art Museum, slides a framed page of the Archimedes parchment into a holder that moves in front of the x-ray beam like a book being read by a stationary eye. (Photo by Diana Rogers)

An early transcription of Archimedes' mathematical theories has been brought to light through the probing of high-intensity x-rays at SSRL's BL6-2. The text contains part of the Method of Mechanical Theorems, one of Archimedes' most important works, which was probably copied out by a scribe in the tenth century. The parchment on which it was written was later scraped down and reused as pages in a twelfth century prayer book, producing a document known as a palimpsest (which comes from the Greek, meaning 'rubbed smooth again'). Some of the text has been read previously, using everything from magnifying glasses to ultraviolet light, which highlights the hidden ink. Some of the text has been solidly obscured by some twentieth-century forgeries of medieval art that were slapped on top of a few pages. Working with curators at the Walters Art Museum and collaborators at Stanford University, SSRL staff scientist Uwe Bergmann suggested using synchrotron x-rays to peer through the forgeries. When hit by the x-rays the iron pigment in the original ink fluoresced and allowed researchers to see the text for the first time. Additional articles on the Archimedes palimpsest and how x-rays read medieval ink can be found at: http://www-ssrl.slac.stanford.edu/research/archimedes_summary.html

4.   Fallen Tree Interrupts User Operations for Several Days

Shortly before 8 a.m. on Wednesday, May 18, a 100-foot pine tree growing in the wooded Skyline hills west of the laboratory snapped off at its base and severed two of the three 230 kilovolt transmission lines providing power to SLAC. This immediately halted all electric power to the entire SLAC site for three days. All users and staff, except those designated for essential safety and maintenance work, were asked to stay away from the site during the outage. Following a very smooth and safe restart of the SPEAR3 accelerator, user operations had resumed on most SSRL beam lines by Monday, May 23. http://news-service.stanford.edu/news/2005/may25/slac-052505.html (Photo courtesy of CEF)

5.   DOE Site Review of SLAC in Washington DC
      (contact: Keith Hodgson, hodgson@ssrl.slac.stanford.edu)

On May 27, SLAC presented its plans for the coming decade to the DOE Office of Science. Representing SLAC at the meeting in Washington were Jonathan Dorfan, Persis Drell, John Galayda, Keith Hodgson and Mimi Chang. Attendees from DOE-SC included Raymond Orbach (Director of DOE-SC), Pat Dehmer, Ari Patrinos, and Robin Staffin (Directors of the 3 offices primarily responsible for funding that comes into SLAC) as well as a number of other DOE officials. As with each of the other DOE-SC labs making these presentations, SLAC described strategic future in terms of a business plan - its strategic business units, core competencies and supporting initiatives. SLAC stressed that the most important single element in the near future was the on-time and on-budget completion of the LCLS and the delivery of the performance of this remarkable new light source. In the photon science area, the SSRL program on SPEAR3 was stressed as providing a strong complementary component - which together will position the laboratory to have world leading capabilities by 2009. Significant time was also devoted to the evolution and future of the particle and particle astrophysics programs and the vision that they will remain a strong piece of the SLAC science portfolio. Overall, we felt that the business case for SLAC was communicated well and DOE-SC gained a better understanding of the important assets and future science opportunities at SLAC.

6.   Keith Hodgson Named Deputy Director of SLAC

Last week, SLAC announced a major reorganization of the structure and senior management of the laboratory, which Stanford University has operated for more than 40 years for the U.S. Department of Energy. The new organizational structure is built around four new directorates -- Photon Science, Particle and Particle Astrophysics, Linac Coherent Light Source (LCLS) Construction and Operations. Keith Hodgson has been named as a Deputy Director of SLAC and as Director of the Photon Science Directorate, with responsibility for the Stanford Synchrotron Radiation Laboratory (SSRL), the science and instrument program for the LCLS (the world's first x-ray free electron laser) and the new Ultrafast Science Center. Keith's counterpart in Particle and Particle Astrophysics is Persis Drell (Persis also holds the title of Deputy Director of SLAC). For further information, see: http://www.slac.stanford.edu/gen/pubinfo/pr/20050525/

7.   DOE Review of LCLS Project and Proposed LUSI Project
       (contacts: John Galayda, LCLS Project Director, galayda@slac.stanford.edu; John Arthur, LUSI Project Director, jarthur@slac.stanford.edu)

On May 10-12, the DOE Office of Science (DOE/SC) carried out an Independent Review of the Linac Coherent Light Source (LCLS) Project. As part of DOE/SC policy, such reviews are carried out every six months, and cover technical, cost, schedule, and management aspects of the $379M project. The review team included experts on electron accelerator systems, x-ray optics, controls, conventional construction, project management and project safety.

In addition, this review included a look at the proposed LCLS Ultrafast Science Instruments (LUSI) Project, which expects to build most of the instruments that will be used to do cutting-edge science with the LCLS x-ray pulses. This project is in its formative stage, seeking DOE/SC approval for funding in the near future. The LCLS expects to enter its operational phase in the spring of 2009, producing extremely brief but incredibly bright pulses of x-rays: approximately as many x-ray photons as are delivered by an SSRL beam line in one second will be delivered to an LCLS experiment in about 100 femtoseconds (one hundredth of a trillionth of a second). It will offer a unique scientific tool for studying the ultrafast processes that occur on an atomic scale.

The reviewers were pleased with the rapid increase in LCLS staffing levels and the award of long-lead procurements for the undulator systems. The long-lead procurements comprise a limited set of construction activities approved by DOE for FY2005. At the next review, scheduled for December 2005, the LCLS Project will seek Critical Decision 3: approval to begin LCLS construction on all fronts.

• http://www-ssrl.slac.stanford.edu/lcls/
• http://www-ssrl.slac.stanford.edu/lcls/lusi/
• http://www-ssrl.slac.stanford.edu/ultrafast/index.html

8.   Director of OSTP Visits SLAC

Dr. John Marburger, Director of the Office of Science and Technology Policy (OSTP) and Science Advisor to President Bush visited SLAC on May 23. During his visit he was briefed on the new SLAC organizational structure and on the SLAC science programs and their changing balance as the lab builds and brings LCLS into operation. He was given a tour that included stops at the SPPS, the future site for the LCLS, and the GLAST detector (currently in assembly). More information on OSTP can be found at: http://www.ostp.gov/

9.   Axel Brunger Elected to National Academy of Sciences

Axel T. Brunger, Professor of SSRL, Molecular and Cellular Physiology, and Neurology and Neurological Sciences, Stanford University, and a Howard Hughes Medical Institute Investigator, was elected Member of The National Academy of Sciences on May 3, 2005, in recognition of his distinguished and continuing achievements in original research, especially in the area of neurotransmission. Recent results on botulinum neurotoxins were published in the December 16, 2004 edition of Nature and also made the subject of an SSRL science highlight in December 2004 (http://www-ssrl.slac.stanford.edu/research/highlights_archive/cnt.html). Information on other Brunger group projects and publications can be found on the Brunger Lab website: http://atb.slac.stanford.edu

See also: The National Academies article
http://www4.nationalacademies.org/news.nsf/isbn/05032005?OpenDocument

10.   Spring Meeting of the SLAC Scientific Policy Committee
      (contact: Keith Hodgson, hodgson@ssrl.slac.stanford.edu)

The spring 2005 meeting of the SLAC Scientific Policy Committee (SPC) took place May 13-14. The SPC, which reports to Stanford President John Hennessy, is the highest level advisory board for science programs and policy at SLAC. Several new members were welcomed to the committee including Martin Blume (American Physical Society), William Brinkman (Princeton University), Reinhard Brinkmann (DESY), Helmut Dosch (Max Planck Institute for Metallforschung), Craig Hogan (University of Washington), Young-Kee Kim (The University of Chicago and the Enrico Fermi Institute) and Jeff Richman (University of California, Santa Barbara).

SLAC Director Jonathan Dorfan, Keith Hodgson and Persis Drell gave presentations that related to "The Changing Landscape at SLAC - The next Ten Years". Also related to photon science, Jo Stöhr gave a report on the near and longer-term plans for SPEAR3. John Galayda, Jerry Hastings and Mark Reichanadter followed with updates on the LCLS construction and experimental program. The photon science portion of the program concluded with an update by Gordon Brown on SSRL faculty development.

11.   Machine Readable Passports Required for All Visa Waiver Program Travel as of June 26, 2005

The Department of Homeland Security (DHS) is reminding travelers from 27 Visa Waiver Program (VWP) countries that as of June 26, 2005, they must have a machine-readable passport to enter the United States without a visa, as mandated by Congress. Machine-readable passports have a sequence of lines that can be swiped by U.S. Customs and Border Protection (CBP) officers to confirm the passport holder's identity quickly and to obtain other information about the holder typically found on a passport's inside cover.

Sample of machine readable passport

Beginning June 26, 2005, transportation carriers will be fined $3,300 per violation for transporting any VWP traveler to the United States without a machine-readable passport. Similarly, VWP travelers arriving in the United States on that date without a machine-readable passport should not anticipate being granted entry into the country.

http://www.ds-osac.org/Reports/report.cfm?contentID=29100

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SSRL Headlines is published electronically monthly to inform SSRL users, sponsors and other interested people about happenings at SSRL. SSRL is a national synchrotron user facility operated by Stanford University for the U.S. Department of Energy Office of Basic Energy Sciences. Additional support for the structural biology program is provided by the DOE Office of Biological and Environmental Research, the NIH National Center for Research Resources and the NIH Institute for General Medical Sciences. Additional information about SSRL and its operation and schedules is available from the SSRL WWW site.

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	Last Updated:	31 MAY 2005
	Content Owner:	L. Dunn
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